Thrombocytopenic purpura without anemia and leukopenia in Gaucher''s disease

A patient with Gaucher’s disease is described who had thrombocytopenic purpura, but no anemia or leukopenia and only slight enlargement of the spleen.The hemorrhagic diathesis and platelet count responded well to splenectomy.

Submitted on March 2, 1955 Accepted on May 30, 1955     

Susceptibility to thrombosis in normal young,aging, cortisone-treated,heparinized and x-irradiated hamsters as tested by topical application of thrombin

1. Thrombin applied topically to the everted cheek pouch of the hamsterproduced platelet and not red thrombi in exposed, uninjured blood vessels withcirculating blood. Red thrombi were produced in stagnant blood. Thrombusformation occurred in the venules for the most part and seldom in arterioles orcapillaries.

2. An in vivo test for platelet thrombus susceptibility, based on the thrombinreaction and the resistance of the hamster to thrombosis, has been described.

3. Thrombus susceptibility, measured by the thrombin test, increased withage and during cortisone treatment, and decreased after heparin injection andfollowing large doses of whole body x-irradiation.

4. The thrombin susceptibility test could be correlated with the platelet countin x-irradiated hamsters, showing a relatively critical minimum concentrationof blood platelets (100,000/cu.mm.) required for platelet thrombosis.

5. The relationship of platelet concentration to platelet thrombus formationand predisposition to hemorrhage has been discussed.

Submitted on December 6, 1954 Accepted on January 27, 1955     

Platelet thrombosis in human hemostasis; a histologic study of skin wounds in normal and purpuric individuals

The histologic appearance of human skin puncture wounds obtained at biopsy,after measurement of the local bleeding times, has been studied in serial section in3 patients with normal hemostasis and in 4 patients with idiopathic thrombocytopenic purpura. It is found that agglutinated platelets arrest hemorrhage in normalskin by rapidly sealing the mouths of all cut vessels larger than capillaries. Suchplatelet thrombi can resist the effective blood pressure in a cut arteriole of 55micra. The puncture tract is normally filled with red cell-fibrin clot into which theplatelet thrombi protrude. The red clot seals the mouth of the few opened capillaries which can be identified. Other capillaries may be sealed by endothelialagglutination. Fibrin does not enter or form within the injured vessels.

Platelet thrombosis does not occur in idiopathic thrombocytopenic purpura.When larger arterioles and venules are cut the bleeding time is greatly prolongedand fibrin fails to form within the wound because of the speed of blood flow.When smaller vessels are cut in purpura the bleeding time is moderately prolonged,but the cut vessels are eventually sealed by fibrin alone. In thrombocytopenicpurpura the bleeding time is normal if only capillaries are cut, since these arenormally sealed by fibrin.

The similarity of the histologic appearance of human puncture wounds to thatdescribed after experimental vascular injury in other mammals, suggests considerable similarity in mammalian hemostatic mechanisms.

Clinical bleeding time tests vary greatly in depth of puncture and in the caliberand number of the vessels cut. Sufficient volume of hemorrhage during the firstminute is thought to be the best guide to an adequate test of the entire hemostaticmechanism.

     

Homozygous hemoglobin C disease in siblings: further comment on intraerythrocytic crystals

1. Two Negro brothers with homozygous hemoglobin C disease are reported.In one splenectomy was performed.

2. Intraerythrocytic crystals in smears of peripheral blood were demonstratedonly in the patient who had splenectomy. The crystals could not be found inre-examination of bone marrow preparations of this patient that were madeprior to splenectomy.

3. Absence of the spleen may be a necessary factor for the formation of thesecrystals.

4. The presence of homozygous C disease is compatible with a normal lifespan.

Submitted on May 23, 1955 Accepted on October 14, 1955     

A Study of Thrombocytopenia: New Histologic Criteria for the Differentiation of Idiopathic Thrombocytopenia and Thrombocytopenia Associated with Disseminated Lupus Erythematosus

Sixty-nine cases of thrombocytopenia in which splenectomy had been performed have been reviewed. New cytological criteria are described for thediagnosis of disseminated lupus erythematosus by the examination of thesplenic tissue.

Six cases of thrombocytopenia associated with the ingestion of drugs andeight with infectious diseases responded promptly and permanently to splenectomy. The thrombocytopenia associated with disseminated lupus erythematosus (in 16 cases) and idiopathic thrombocytopenic purpura (in 39 cases)had a much more variable response. Approximately three-fifths of patients ineach group had a remission sustained for at least 12 months following splenectomy. In general those patients who had thrombocytopenia for more thanone year before surgery were less likely to respond to splenectomy.

Submitted on November 19, 1966 Accepted on February 8, 1967     

The role of allergy in the pathogenesis of purpura and thrombocytopenia

It has been suggested that, for purposes of etiologic investigation, thrombocytopenic purpura be separated into its two component parts, thrombocytopenia andpurpura, and that they be regarded as two coexisting abnormalities rather thanas a single disease. Historical review of the development of knowledge of the pathogenesis of purpura emphasizes the importance and soundness of this dual approach.Both thrombocytopenia and purpura have been shown to have a complex etiologicpattern with multiple potential etiologic factors. The curious similarity of thesetwo groups of factors may at least partially explain the frequent coexistence of thetwo abnormalities in the clinical picture of thrombocytopenic purpura.

It has been shown that allergy has long been recognized as an etiologic factorof major importance in both purpura and thrombocytopenia. It is logical, therefore, that it should frequently be an important etiologic factor when the two conditions exist together, and it is suggested that when diagnostic methods are moreadequate a considerable number of cases of "idiopathic" thrombocytopenic purpurawill fall into that category and will yield therapeutically to a proper allergic approach.

     

Splenectomy in far-advanced Hodgkin''s disease; report of five cases

Five patients with far-advanced Hodgkin’s disease and with evidence of hematopoietic failure were treated by splenectomy in order to determine whether: (1)the course of the disease could be modified, (2) the hematologic picture improved,and (3) responsiveness to nitrogen mustard or x-ray therapy restored. These patients showed a transient slight improvement in their hematologic status, butthe course of the disease possibly was accelerated, and the patients all diedwithin thirteen weeks, without showing renewed suitability or increased responsiveness to therapy.

On the basis of our data and a review of thirty cases from the literature, it isconcluded that splenectomy is not a useful procedure its Hodgkin’s disease, exceptfor certain specific indications. These may be: (1) an apparently solitary splenictumor; (2) acquired hemolytic anemia, although this process may be better controlled in some cases by treating the underlying Hodgkin’s disease with x-rays,nitrogen mustard, or triethylene melamine ; (3) thrombocytopenic purpura,which appears to be more profound than is to be expected from the severity andextent of Hodgkin’s disease; and (4) hypersplenism. Hematopoietic depressionin the vast majority of patients with Hodgkin’s disease, however, cannot beattributed to splenic overactivity or malfunction.

Submitted on October 23, 1953 Accepted on December 17, 1953     

Detection of platelet antibodies in idiopathic thrombopenic purpura

The authors report the results of Dixon's assay modified by Follea in 24 cases of idiopathic thrombocytopenic purpura. The level of immunoglobulin G bound to platelet membrane was increased in 91 p. 100 of patients in the acute phase of the disease. An inverse correlation was demonstrated between platelet-bound antibody levels and platelet count as well as platelet survival. In all cases of refractory idiopathic thrombocytopenic purpura, the assay was positive and the mean level was higher. When the platelet count improved after prednisone therapy or after splenectomy, the level decreased. Platelet antibody determination seems to be useful for predicting the course of the disease. Patients with normal immunoglobulin G bound to platelet might have only C3, IgM or IgA. Dixon's assay is not specific to idiopathic thrombopenic purpura, since it is positive in other types of thrombocytopenia, but immunoglobulin G bound to platelet probably represents specific antiplatelet antibodies.     

A clinical study of bubonic plague. Observations of the 1970 Vietnam epidemic with emphasis on coagulation studies, skin histology and electrocardiograms

Clinical features of forty patients with bacteriologically-proved bubonic plague are described. Adolescents with severe clinical illness predominated. All patients were treated with streptomycin; only one patient died. Fifteen patients were toxic and had a higher mean white cell count, a lower mean platelet count and a higher mean serum glutamic oxaloacetic transaminase level (SGOT) than the others. Eleven patients had evidence for disseminated intravascular coagulation (DIC) based on low platelet counts, prolonged partial thromboplastin times and positive ethanol gelation tests. Skin biopsy specimens from two of these with purpura revealed intravascular fibrin thrombi in dermal vessels. Two patients had electrocardiograms showing right axis deviation that suggested acute cor pulmonale. These findings of laboratory evidence for DIC, fibrin thrombi in purpuric lesions and acute cor pulmonale are explained by known actions of endotoxin and support the concept that endotoxin by mediating a generalized Shwartzman reaction plays a major role in the pathogenesis of plague.     

Isoimmune Neonatal Thrombocytopenic Purpura: Clinical and Therapeutic Considerations

1. Serologic tests utilizing complement fixation have allowed differentiationof isoimmune neonatal thrombocytopenia from other forms of congenitalthrombocytopenia.

2. The pathogenesis of the isoimmune disease involves fetal-maternal incompatibility of platelet antigens, and destruction of fetal platelets by atransplacental transfer of maternal antibody.

3. Three different platelet antigens have been implicated in neonatalpurpura. None of these antigens correspond to known erythrocyte antigens,but two of the platelet antigens are shared by granulocytes and lymphocytes.

4. Review of the literature of probable isoimmune neonatal purpura andour own cases reveals that in untreated cases death occurs in approximately12 per cent of cases, and platelet counts usually do not remain below 60,000/mm.³ longer than 21 days.

5. In two of three instances in which neonatal thrombocytopenia was anticipated as a result of serologic tests done on the mothers, antepartum steroidsmay have benefited the infant.

6. Steroid therapy to the infant appears to shorten the duration of thrombocytopenia, and in one instance exchange transfusion led to immediate cessation of hemorrhage and rapid return of platelets to normal.

Submitted on June 13, 1963 Accepted on August 12, 1963     

Autoimmune Thrombocytopenic Purpura ("ITP" Type) with Chronic Lymphocytic Leukemia

Five cases of chronic lymphocytic leukemia complicated by thrombocytopenic purpura are presented. They differed from the usual cases with thiscomplication in that megakaryocytes were plentiful in spite of leukemic involvement of the bone marrow. Hypersplenism did not appear to be a factor.

The evidence suggests that the thrombocytopenia was of an autoimmunenature, due to antiplatelet antibodies. Brief platelet survival times, the presenceof a platelet agglutinin, staining of megakaryocytes by fluorescein-labeledanti-human globulin, and responses to corticosteroids were demonstrated.

Submitted on March 6, 1961 Accepted on September 28, 1961     

Thrombotic thrombocytopenic purpura; hemorrhagic diathesis with generalized platelet thromboses

1. "Thrombotic thrombocytopenic purpura" is the name which we propose fora rare but well-defined disorder which manifests itself clinically as an acute febrileillness and which is characterized by (a) petechiae and ecchymoses, thrombocytopenia, prolonged bleeding time and poor clot retraction, (b) by a severe anemia outof proportion to any observed blood loss, (c) by mild acholuric jaundice, hepato-splenomegaly, (d) by bizarre and intermittent mental and neurologic symptomsand signs, and (e) by a transient leukemoid reaction in the peripheral blood.

2. This clinical picture must be correlated with a remarkable histologic pattern,namely the presence of myriads of platelet thrombi in the small arterioles andcapillaries of almost all organs of the body.

3. Eleven such cases have been described in the literature. One case of our ownis added.

4. The clinical features of this disease are detailed and the differential diagnosisis discussed. It is emphasized that if the physician is familiar with this syndromea correct clinical diagnosis may become readily possible.

Note: Acknowledgment for the support of this work is made to the Hulda B. and Maurice L. RothschildFoundation for Scientific Research.

     

Low fetal morbidity in pregnancy associated with acute and chronic idiopathic thrombocytopenic purpura

Forty-six mothers with immune thrombocytopenic purpura (ITP) gave birth to 72 babies. Sixty-two babies were delivered vaginally and 10 babies by cesarean section. There was no mortality among mothers or babies. Eighteen infants were born thrombocytopenic (PLT < 100 ± 10⁹/l). Eleven infants had a platelet count of less than 50 ± 10⁹/l. All the severely thrombocytopenic babies (except 1) were born to post splenectomy thrombocytopenic mothers, regardless of steroid treatment during pregnancy. Five babies had clinical manifestations of bleeding; 3 had mild purpura, 1 severe gastrointestinal bleeding, and 1 intracranial bleeding. The latter 2 babies were born prematurely to the same mother who was severely thrombocytopenic despite splenectomy in childhood. In view of very low morbidity in babies of ITP mothers, we suggest that they be delivered vaginally. Cesarean delivery should be performed in selected cases where the mother is severely thrombocytopenic despite splenectomy or where prematurity or obstetrical complications are encountered. © 1994 Wiley-Liss, Inc.     

Thrombotic thrombocytopenic purpura in a previously splenectomized patient

Idiopathic thrombocytopenic purpura was diagnosed in a 26 year old man who had rectal bleeding and marked thrombocytopenia (10,000 platelets/mm³). Complete recovery followed treatment with steroids and splenectomy. There was no clinical, laboratory or histopathologic evidence of thrombotic thrombocytopenic purpura. Several months later typical thrombotic thrombocytopenic purpura developed; recovery followed treatment with steroids, aspirin and dipyridamole. The presence of Howell-Jolly bodies and a negative scan indicated that an accessory spleen was not present. Since thrombotic thrombocytopenic purpura developed in the absence of a spleen in this case, it may be that in some, if not all, instances of thrombotic thrombocytopenic purpura the spleen is not importantly related to the pathogenesis of thrombotic thrombocytopenic purpura; this is in contrast to the situation in idiopathic thrombocytopenic purpura. Benefits attributed to splenectomy in thrombotic thrombocytopenic purpura, therefore, may in fact be due to the platelet inhibitory properties of common anesthetic agents, or to some other factor in the surgical procedure rather than to removal of the spleen per se.     

Plasma exchanges as treatment of severe acute immune thrombocytopenic purpura

INTRODUCTION: High dose steroids and intravenous immunoglobulins are the gold treatment of acute immune thrombocytopenic purpura, before splenectomy for severe and refractory forms of the disease. Authors report two cases of severe acute refractory immune thombocytopenia with a dramatic response to plasma exchanges. EXEGESIS: The first case was an idiopathic form, complicated by hemorragic peritoneal effusion. After failure of steroids, intravenous immunoglobulins and splenectomy and 2 courses of rituximab, plasmapheresis normalized in 3 days platelet count. In the second observation, ITP was associated to systemic lupus with antiphospholipids antibodies and multivisceral failure, despite steroids and intravenous immunoglobulins. After 3 plasma exchanges, platelet count was normalized, and the patient is under remission after 24 months follow-up. CONCLUSION: Plasmapheresis must be evaluated as an emergency treatment in refractory forms of acute immune thrombocytopenic purpura.     

Splenectomy and extravascular platelet destruction in thrombotic thrombocytopenic purpura

Intravascular platelet deposition has been considered an essential pathophysiologic mechanism in thrombotic thrombocytopenic purpura. Splenectomy resulted in prompt and sustained hematologic improvement in a patient with the chronic form of the disease. The response to splenectomy, normal plasma levels of secretable platelet proteins, and phagocytosis of erythrocyte fragments and platelets by splenic macrophages demonstrated by electron microscopy suggest that platelet destruction may occasionally be predominantly extravascular in this disease.     

CHRONIC NEUTROPENIA: REPORT OF A CASE NOT CURED BY SPLENECTOMY

A case of severe chronic neutropenia without splenomegaly is reported. Thedisorder was characterized by chronic fatigue and many pyogenic infections, andby a persistently low neutrophile count. The marrow was cellular, with a defectin maturation in both granulocytic and megakaryocytic series. There was noimprovement on the usual types of medical therapy, and splenectomy, while it wasfollowed by transient thrombocytosis, likewise failed to induce a remission.

It is suggested that in the consideration of therapy for severe neutropenia, a lackof splenomegaly should be considered a contraindication to splenectomy.

     

Syndrome of hypogammaglobulinemia,splenomegaly and hypersplenism

Two cases of acquired idiopathic hypogammaglobulinemia associated withsplenomegaly and hemolytic anemia due to hypersplenism have been reported.Splenomegaly and hypersplenism appears to be the result of reticulum cellhyperplasia caused by the lack of gamma globulin and resultant repeated infections. Both the cases had splenectomy with marked hematologic improvement.

A review of the literature indicates that this syndrome is relatively common,in comparison to the incidence of total number of acquired hypogammaglobulinemia that has been reported in the literature so far. It also seems veryimportant to recognize it because of the obvious therapeutic implications. Serumgamma globulin level should be determined in cases with unexplained hepatosplenomegaly, hypersplenism and hemolytic anemia.

Submitted on February 9, 1957 Accepted on July 1, 1957     

The site of platelet destruction in thrombocytopenic purpura as a predictive index of the efficacy of splenectomy

The significance of the site of platelet sequestration in determining the indication for splenectomy in idiopathic thrombocytopenic purpura (ITP) is a controversial subject. However, most of the negative conclusions are based on 51chromium labelling of homologous platelets. We report here the results of an analysis of 222 cases in which the kinetic study of 111indium-oxinate-labelled autologous platelets was performed under homogeneous technical conditions. 103 of these patients subsequently underwent splenectomy. This study demonstrates that the site of platelet sequestration in active ITP constitutes a variable independent of the patient's age, history of the disease and its severity (platelet count, lifespan). The sequestration site is a good predictive element of the short-term efficacy of splenectomy (71/76 cases with splenic sequestration obtained a platelet count exceeding 100 x 10(9)/l versus 7/13 cases with mixed sequestration and 1/14 cases with hepatic sequestration), and the long-term results (6 months to 5 years after splenectomy) do confirm the clinical value of this study.     

Thrombotic Thrombocytopenic Purpura in Childhood

(1) Two cases of thrombotic thrombocytopenic purpura (TTP) occurring inchildhood are described. Case 1 is unique in that the patient survived for 12years.

(2) The clinical features of 19 reported cases of TTP in children are reviewed.

(3) The presence of morphologic abnormalities of red blood cells and theregular occurrence of kidney involvement in this disorder is emphasized. Inone patient (Case 2), histologic changes of the disease were limited to the kidney.

(4) Certain hematologic and histologic features shared by TTP and eclampsia are described.

(5) Unusual histologic lesions of renal vessels are described.

Submitted on June 20, 1961 Accepted on November 3, 1961